The use of isotopes in the determination of absolute bioavailability of drugs in humans
- 30 May 2006
- journal article
- review article
- Published by Informa Healthcare in Expert Opinion on Drug Metabolism & Toxicology
- Vol. 2 (3), 419-427
- https://doi.org/10.1517/17425255.2.3.419
Abstract
Absolute bioavailability studies in humans are not routinely performed as part of the drug registration process. They tend to be reasonably demanding, not least because toxicology data are required to support intravenous administration of a drug. Moreover, the classical crossover design of an absolute bioavailability study can suffer from artefacts caused by concentration-dependent pharmacokinetics. Many of the problems associated with absolute bioavailability studies can be alleviated using isotopically labelled drugs. Stable isotopes have been used in the performance of absolute bioavailability studies in humans for > 30 years. More recently, the advantages of using radiolabelled drugs have been expanded by using the ultrasensitive technology of accelerator mass spectrometry. Isotopic labelling not only allows for the accurate and efficient determination of absolute bioavailability, but can also provide information on first-pass effects and other pharmacokinetic parameters. © 2006 Informa UK LtdKeywords
This publication has 29 references indexed in Scilit:
- The use of isotope effects to determine enzyme mechanismsArchives of Biochemistry and Biophysics, 2005
- Bioavailability and Bioequivalence: An FDA Regulatory OverviewPharmaceutical Research, 2001
- Calculation of isotope effects from first principlesBiochimica et Biophysica Acta (BBA) - Bioenergetics, 2000
- Gas Uptake Studies of Deuterium Isotope Effects on Dichloromethane Metabolism in Female B6C3F1 Mice in VivoToxicology and Applied Pharmacology, 1994
- Bioavailability Studies of Drugs with Nonlinear Pharmacokinetics: II. Absolute Bioavailability of Intravenous Phenytoin Prodrug at Therapeutic Phenytoin Serum Concentrations Determined by Double‐Stable Isotope TechniqueThe Journal of Clinical Pharmacology, 1993
- Concurrent intravenous administration of a labeled tracer to determine the oral bioavailability of a drug exhibiting Michaelis-Menten metabolismJournal of Pharmacokinetics and Biopharmaceutics, 1987
- Carbon isotope effect on carboxylation of ribulose bisphosphate catalyzed by ribulose bisphosphate carboxylase from Rhodospirillum rubrumBiochemistry, 1985
- Theoretical considerations in the calculation of bioavailability of drugs exhibiting Michaelis-Menten elimination kineticsJournal of Pharmacokinetics and Biopharmaceutics, 1984
- Nonlinear assessment of phenytoin bioavailabilityJournal of Pharmacokinetics and Biopharmaceutics, 1976
- Absolute bioavailability in man of N‐acetylprocainamide determined by a novel stable isotope methodClinical Pharmacology & Therapeutics, 1975